Iron oxide nanoparticles crossing a cell membrane.

Iron's New Ride: How Nanoparticles Are Revolutionizing Iron Delivery

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Mira Elwood in Health & Wellness September 2025 • 4 min read.

"Scientists uncover how iron oxide nanoparticles bypass traditional cell entry, offering hope for better iron supplements and targeted therapies."


Iron deficiency remains a significant global health challenge despite ongoing efforts to improve iron supplementation and food fortification. A key obstacle is the poor tolerability of conventional iron salts, resulting in low adherence and limited effectiveness in addressing iron deficiency anemia. This has spurred the search for alternative iron delivery methods, with nanoformulations emerging as a promising avenue for fortifying food and feed.

For years, scientists believed that nanoparticles (NPs) could only enter cells through endocytosis, a process where the cell membrane engulfs the particle. However, recent studies suggest that certain NPs might bypass this route, directly crossing the plasma membrane to access the cytoplasm. This novel pathway could revolutionize how we deliver iron and other therapeutic agents at the cellular level.

In a new study, researchers investigated how iron nanoparticles are taken up by cells, focusing on the possibility of direct membrane crossing. Using a sophisticated protocol to track cytoplasmic iron concentration dynamics, they've uncovered compelling evidence that certain iron oxide NPs can indeed cross the plasma membrane, opening exciting new possibilities for targeted iron delivery and cellular therapies.

Bypassing the Gatekeepers: How Iron Oxide Nanoparticles Enter Cells

Iron oxide nanoparticles crossing a cell membrane.

The research team used Xenopus laevis oocytes (frog egg cells) as a model to study the uptake of different types of iron nanoparticles: iron oxide (Fe3O4) and zerovalent iron (Fe). These oocytes were modified to express DMT1, a protein that facilitates iron transport. The researchers then monitored changes in the cells' internal iron concentration using a fluorescent indicator called Calcein.

Their findings revealed a striking difference between the nanoparticles. Iron oxide NPs were able to significantly increase the intracellular iron concentration, indicating they had successfully entered the cells. However, zerovalent iron NPs failed to do so, suggesting a different mechanism or a barrier to entry. Further experiments showed that when iron oxide NPs were aggregated (clumped together) or coated with a protein 'corona' (bovine serum albumin), their ability to cross the membrane was also inhibited.

  • Iron Oxide NPs: Successfully cross cell membranes, increasing intracellular iron.
  • Zerovalent Iron NPs: Unable to cross cell membranes.
  • Aggregated or Coated NPs: Crossing inhibited, highlighting the importance of NP characteristics.
To understand how iron oxide NPs were entering the cells, the researchers used electrophysiology – a technique that measures the electrical properties of cell membranes. They discovered that when iron oxide NPs interacted with the cell membrane, there was a small, transient increase in membrane conductance. This suggests that the NPs were creating temporary pores or disruptions in the membrane to facilitate their passage.

A New Frontier in Iron Delivery and Cellular Therapies

This study provides compelling evidence that iron oxide nanoparticles can directly cross cell membranes, bypassing the traditional endocytosis pathway. This discovery has significant implications for improving iron supplementation and developing targeted therapies for various diseases.

The ability to deliver iron directly into cells could lead to more effective treatments for iron deficiency anemia, reducing the side effects associated with conventional iron salts. Furthermore, this approach could be extended to deliver other therapeutic agents, such as drugs or genes, directly into cells, opening new avenues for treating cancer, genetic disorders, and infectious diseases.

While further research is needed to fully understand the mechanisms and potential applications of this novel pathway, these findings represent a major step forward in the field of nanomedicine. By harnessing the unique properties of nanoparticles, we can revolutionize how we deliver essential nutrients and treat diseases at the cellular level, paving the way for a healthier future.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1038/s41598-017-11535-z, Alternate LINK

Title: Iron Oxide Nanoparticles Can Cross Plasma Membranes

Subject: Multidisciplinary

Journal: Scientific Reports

Publisher: Springer Science and Business Media LLC

Authors: Daniele Zanella, Elena Bossi, Rosalba Gornati, Carlos Bastos, Nuno Faria, Giovanni Bernardini

Published: 2017-09-12

Everything You Need To Know

1

What is the new method scientists discovered for iron delivery?

Scientists have discovered that iron oxide nanoparticles can directly cross cell membranes, a route that bypasses the traditional endocytosis process. This groundbreaking finding suggests a more efficient way to deliver iron at the cellular level.

2

How do iron oxide nanoparticles and zerovalent iron nanoparticles differ in their ability to enter cells?

The research indicates that iron oxide nanoparticles can significantly increase intracellular iron concentration by directly crossing the plasma membrane. In contrast, zerovalent iron nanoparticles were found to be unable to cross cell membranes, suggesting a different uptake mechanism or a barrier to entry. Additionally, when iron oxide nanoparticles were aggregated or coated with a protein 'corona' (bovine serum albumin), their ability to cross the membrane was inhibited.

3

What methods did researchers use to study how iron nanoparticles are taken up by cells?

The researchers used Xenopus laevis oocytes (frog egg cells) modified to express DMT1, a protein that facilitates iron transport, as a model to study the uptake of iron nanoparticles. They monitored changes in the cells' internal iron concentration using a fluorescent indicator called Calcein and electrophysiology, a technique that measures the electrical properties of cell membranes. These methods helped them observe how different nanoparticles interact with and cross cell membranes.

4

What are the broader implications of discovering that iron oxide nanoparticles can directly cross cell membranes?

This research has significant implications for improving iron supplementation and developing targeted therapies. The direct membrane crossing of iron oxide nanoparticles allows for more efficient and targeted iron delivery, potentially overcoming the limitations of traditional iron salts, such as poor tolerability and low adherence. This could lead to better treatments for iron deficiency anemia and other diseases at the cellular level. This may lead to advancements in various cellular therapies.

5

How do iron oxide nanoparticles manage to cross cell membranes, according to the research?

The study found that iron oxide nanoparticles create temporary pores or disruptions in the cell membrane to facilitate their passage. These disruptions were detected through electrophysiology, which measured a small, transient increase in membrane conductance when iron oxide nanoparticles interacted with the cell membrane. This suggests a physical mechanism where the nanoparticles directly interact with the lipid bilayer to gain entry.

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